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. 2022 Aug 12;31(10):1477–1499. doi: 10.1111/exd.14655

TABLE 2.

YAP/TAZ‐TEAD inhibitors of protein–protein interaction, surface binding

Molecule Other name(s) Inhibitory action Binding validation Activity validation Interface Binding affinity (KD) IC50 References Vendor
TB1G1/TB1G2 Cysteine‐dense peptide (CDP) iPPI Rosetta protein design, mammalian surface display, SPR, Co‐IP, PLA TEAD luciferase reporter, competitive mammalian surface display 2

TB1G1: 31 ± 2 nM

TB1G2: 368 ± 4 pM

 NR 240
Fragment 1 iPPI scaffold Co‐crystal structure ITC, TEAD luciferase reporter 2 ~300 μM NR 241 Chemspace (#CSSB00000239375)
Peptide 17 YAP‐TEAD inhibitor 1 iPPI Molecular docking, co‐crystal structure, pull‐down assay Pull‐down assay 3 15 nM 25 nM 242

Selleckchem (#S8164)

AdooQ (#A15858)

APExBIO (#A1149)

MedChemExpress (#HY‐P2244)
Peptide 10 iPPI Co‐crystal structure, SPR Pull‐down assay 3 289.5 nM 297 nM 243
Peptides 9, 10 iPPI Co‐crystal structure TR‐FRET 3

Peptide 9: 25 nM

Peptide 10: NR

Peptide 9: 16 ± 5 nM

Peptide 10: 9 ± 2 nM

 244
TEAD‐binding fragment MFCD00187673 iPPI scaffold NMR ITC 3 77 nM NR 245

Chemspace

(#CSC000003413)
Dioxo‐benzoisothiazole Example 22 iPPI NMR TEAD luciferase reporter, AlphaLISA® 3 NR 83 nM 246 patented: WO2017064277A1
1,2,3‐Triazole‐4‐carbohydrazide derivatives (hit 2) iPPI Molecular docking, TSA MST, TSA, TEAD luciferase reporter, YAP‐TEAD target gene qPCR 3 650 μM 6.5 μM 247

MCule

(#MCULE‐3696035303)

MolPort

(# MolPort‐002‐604‐580)
Compound 3.1

Pyrazidol,

Pirlindol,

Pirlindolum

 iPPI Molecular docking, STD NMR Co‐IP, TEAD luciferase reporter, pull‐down assay, YAP‐TEAD target gene qPCR 3 ~12 μM 33–44 μM (TEAD isoform‐dependent) 248

Chemspace

(#CSC020600808)
Super‐TDU iPPI Molecular modelling Co‐IP, mutational studies 2&3 NR 57.9 ng/ml 249

Selleckchem (#S8554)

MedChemExpress (#HY‐P1727)

Abbreviations: AlphaLISA, amplified luminescent proximity homogenous assay (linked immunosorbent assay); Co‐IP, co‐immunoprecipitation; iPPI, inhibitor of protein–protein interaction; ITC, isothermal titration calorimetry; MST, microscale thermophoresis; NMR, nuclear magnetic resonance; NR, not reported; PLA, proximity ligation assay; SPR, surface plasmon resonance; STD NMR, saturation transfer difference nuclear magnetic resonance; TR‐FRET, time‐resolved fluorescence resonance energy transfer; TSA, thermal shift assay.